Collapsin response mediator proteins (CRMPs) are cytosolic phosphoproteins involved in neuronal differentiation and axonal guidance. CRMP2 was previously shown to mediate the repulsive effect of Sema3A on axons and to participate in axonal specification. The CRMPs appear to play a complex role in axon growth as well as microtubule dynamics and axon induction. CRMPs localize to the lamellipodia and filopodia of axonal growth cones, suggesting a role in axon guidance. Moreover, CRMP2 is upregulated after axotomy, and appears to increase the formation of axon-type processes from hippocampal neurons. CRMP2 has been reported to bind tubulin dimers directly and modulate microtubule assembly. CRMPs have also been implicated in the pathogenesis of a paraneoplastic neurologic syndrome. Interaction studies have implicated phospholipase D2 (PLD2), the cytosolic tyrosine kinase Fes, and intersectin in CRMP function. Hyperphosphorylation of CRMP2 is an early event in the progression of Alzheimer's disease.